LBPO.PR01 · 预防研究 · Late-Breaking

多祖源全基因组和全转录组关联研究拓展了乳腺癌整体及各亚型的易感性图谱

Multi-ancestry genome- and transcriptome-wide association studies expand the susceptibility landscape for breast cancer overall and across subtypes

编号 LB207 展板 5 时间 4/20 02:00–05:00 区域 Section 54 主讲 Zheng Guo, MD;PhD

分会场 Late-Breaking Research: Prevention, Early Detection, and Interception

该海报暂无可下载的资料 AACR 官方页面

作者与单位 Authors & Affiliations

Zheng Guo¹, Guochong Jia¹, Jie Ping¹, Xingyi Guo¹, Shuai Xu¹, Yulu Zheng¹, Thomas U. Ahearn², Christine Ambrosone³, Montserrat Garcia-Closas², Jian Gu⁴, Christopher A. Haiman⁵, Dezheng Hu⁶, Motoki Iwasaki⁷, Sun-Young Kong⁸, Sun-Seog Kweon⁹, Koichi Matsuda¹⁰, Keitaro Matsuo¹¹, Katherine L. Nathanson¹², Barbara Nemesure¹³, Katie M. O'Brien¹⁴, Olufunmilayo Olopade⁶, Tuya Pal¹, Julie Palmer¹⁵, Sue K. Park¹⁶, Michael F. Press¹⁷, Melissa Troester¹⁸, Song Yao¹⁹, Bingshan Li²⁰, Ran Tao¹, Xiao-Ou Shu¹, Jirong Long¹, Wei Zheng¹

¹Vanderbilt University Medical Center, Nashville, TN,²Institute of Cancer Reserach, Edinburgh, United Kingdom,³Roswell Park Comprehensive Cancer Center, Roswell Park Comprehensive Cancer Center, NY,⁴The University of Texas MD Anderson Cancer Center, Houston, TX,⁵Keck School of Medicine of USC, Los Angeles, CA,⁶University of Chicago, Chicago, IL,⁷National Cancer Center Institute for Cancer Control, Tokyo, Japan,⁸National Cancer Center, Seoul, Korea, Republic of,⁹Chonnam National University Medical School, Hwasun, Korea, Republic of,¹⁰University of Tokyo, Tokyo, Japan,¹¹Aichi Cancer Center Research Institute, Nagoya, Japan,¹²University of Pennsylvania, Philadelphia, PA,¹³Stony Brook University, Stony Brook, NY,¹⁴National Institute of Envrionmental Health Sciences, Durham, NC,¹⁵Boston University, Boston, MA,¹⁶Seoul National University College of Medicine, Seoul, Korea, Republic of,¹⁷USC / Norris Comprehensive Cancer Center, Los Angeles, CA,¹⁸University of North Carolina, Chapel Hill, NC,¹⁹Roswell Park Comprehensive Cancer Center, Buffalo, NY,²⁰Vanderbilt University, Nashville, TN

摘要 Abstract

中文摘要

乳腺癌基因组研究主要在欧洲祖源人群中开展，限制了多样性和统计效力。在本研究中，我们大幅增加了非洲和亚洲祖源女性的代表性，并显著扩大了欧洲后裔的样本量，创建了迄今为止最大的乳腺癌全基因组关联研究（GWAS）多祖源数据集。基于237,817例病例和1,679,059例对照，我们跨祖源开展了GWAS和全转录组关联研究（TWAS），分别在P<5×10⁻⁸（GWAS）和Bonferroni校正后P为1.54×10⁻⁴（TWAS）的水平上，识别出326个风险位点和113个与整体乳腺癌风险相关的基因。其中，153个风险位点和69个基因此前未见报道。针对雌激素受体（ER）阳性、ER阴性和三阴性乳腺癌（TNBC）的亚型特异性分析额外揭示了89个位点和64个与乳腺癌风险相关的基因，包括61个位点和12个此前未报道的基因。此外，25个位点和11个基因的关联因ER状态而存在显著差异，22个位点和8个基因仅与三阴性乳腺癌风险相关。本研究识别出的风险基因在与转录调控、雌激素反应、有丝分裂纺锤体过程和DNA损伤修复相关的通路中显著富集。总之，这些发现大幅拓展了乳腺癌易感性和亚型特异性遗传结构的图谱，并为乳腺癌生物学和遗传学提供了更多见解。

查看英文原文 English abstract

Breast cancer genomic studies have been conducted primarily in European-ancestry populations, limiting both diversity and statistical power. In this study, we substantially increased the representation of African- and Asian-ancestry women and markedly expanded the sample size of European descendants, creating the largest multi-ancestry dataset for breast cancer genome-wide association studies (GWAS) to date. With 237,817 cases and 1,679,059 controls, we conducted GWAS and transcriptome-wide association studies (TWAS) across ancestries and identified 326 risk loci and 113 genes associated with overall breast cancer risk at a P < 5 × 10⁻⁸ (for GWAS) and Bonferroni-corrected P of 1.54 × 10⁻⁴ (for TWAS), respectively. Of them, 153 risk loci and 69 genes were not reported previously. Subtype-specific analyses for estrogen receptor (ER) positive, ER-negative and triple-negative breast cancer (TNBC) revealed an additional 89 loci and 64 genes associated with breast cancer risk, including 61 loci and 12 genes not previously reported. Moreover, associations for 25 loci and 11 genes differed significantly by ER status, and 22 loci and eight genes were exclusively associated with risk of triple-negative breast cancer. Risk genes identified in this study were significantly enriched in pathways related to transcriptional regulation, estrogen response, mitotic spindle processes, and DNA damage repair. Together, these findings substantially expand the landscape of breast cancer susceptibility, subtype-specific genetic architecture, and provide added insights into breast cancer biology and genetics.

利益披露 Disclosure

Z. Guo, None.. G. Jia, None.. J. Ping, None.. X. Guo, None.. S. Xu, None.. Y. Zheng, None.. T. U. Ahearn, None.. C. Ambrosone, None.. M. Garcia-Closas, None.. J. Gu, None.. C. A. Haiman, None.. D. Hu, None.. M. Iwasaki, None.. S. Kong, None.. S. Kweon, None.. K. Matsuda, None.. K. Matsuo, None.. K. L. Nathanson, None.. B. Nemesure, None.. K. M. O'Brien, None.. O. Olopade, None.. T. Pal, None.. J. Palmer, None.. S. K. Park, None.. M. F. Press, None.. M. Troester, None.. S. Yao, None.. B. Li, None.. R. Tao, None.. X. Shu, None.. J. Long, None.. W. Zheng, None.

← 返回 AACR 2026 检索